2. Influenza A H1N1 infection
Clinical management of the
individuals with ILI
Gamal Rabie Agmy ,MD ,FCCP
Professor of Chest Diseases, Assiut University

3. Influenza-Like Illness
Case Definition
 Fever ≥ 38.00 C and a cough &/or a sore
throat in the absence of a known cause
other than influenza
 Clinically may be difficult to differentiate
from other causes of RTI
 However,in pandemic setting more likely
due to influenza A/H1N1
 This definition applies for both adult and
child (a child = less than 12 yrs old).

4. Infectiousness & Incubation period
 Estimated incubation period 1-7 days, [ likely 1-4 days ].
 Infectious period for a confirmed case of influenza A (H1N1)
virus infection is defined as 1 day prior to the case’s illness
onset to 7 days after onset.
 Close contact is defined as: within about 3 feet of an ill person
who is a confirmed or suspected case of influenza A H1N1
virus infection during the case’s infectious period.
 H1N1 appears to be more contagious than seasonal
influenza. The 2° attack rate of seasonal influenza ranges
from 5% to 15%. Current estimates of the 2° attack rate of
H1N1 range from 22% to 33%.

5. Clinical Features of
Influenza A/H1N1
 Clinical Findings
Uncomplicated disease manifest with fever, headache, upper respiratory
tract symptoms (cough, sore throat, rhinorrhea), myalgia, fatigue, vomiting,
or diarrhea.
 Complications
Clinical syndromes have ranged from mild respiratory illness, to lower
respiratory tract illness, dehydration, or pneumonia.
Can expect complications similar to seasonal flu: exacerbation of
underlying chronic medical conditions, URTIs (sinusitis, otitis media, croup)
LRT disease (pneumonia, bronchiolitis, status asthmaticus), cardiac
(myocarditis, pericarditis), musculoskeletal (myositis, rhabdomyolysis),
neurologic (acute & post-infectious encephalopathy, encephalitis, febrile
seizures, status epilepticus), and 2° bacterial pneumonia.
In children,risk of REYE Syndrome (therefore, NSAIDS contraindicated)

6. Symptom
Fever*
223 (83%)
Shortness of breath
145 (54%)
Fatigue/Weakness
108 (40%)
Chills
99 (37%)
Myalgias
96 (36%)
Rhinorrhea
96 (36%)
Sore Throat
84 (31%)
Headache
83 (31%)
Vomiting
78 (29%)
Wheezing
Source: CDC
249 (93%)
Cough
Symptoms
of 268
hospitalized
novel H1N1
patients
(US)
Number (%)
64 (24%)
Diarrhea
64 (24%)

7. Novel Influenza A/H1N1
Infections in Children
 Majority are mild & self limiting
 Most common Sx are fever(100%) ,
cough(100%) , sore throat(66%) ,
myalgia(44%) , vomiting &
diarrhea(25%)
 Uncommon: altered conscious
level(10%) , hypotension
 Mild cases do not need admission or Ix

8. Medical care for patients with
novel influenza A (H1N1) virus
 Not all patients with suspected novel
influenza (H1N1) infection need to be seen by
a health care provider. For most people, the
illness appears to be mild and self-limiting.
 Minority of people with influenza A(H1N1) has
had severe illness with complications. Many, but
not all, have underlying risk factors (comorbidities ) that are likely to have contributed
to the severity of the condition.

9. Complications of Influenza:
 Respiratory
complications are the
most common ones (esp
secondary infections).
 At times these
complications, eg. an
exacerbation of COPD,
may be the presenting
symptom.
 Cardiac events are not
uncommon.
Complications of
influenza
Respiratory
Major clinical category
Pneumonia: primary viral, secondary
bacterial, combined
Upper respiratory: otitis media, sinusitis,
conjunctivitis
Acute laryngotracheo-bronchitis (croup)
Bronchiolitis
Complication of pre-existing disease
Cardiovascular
Myocarditis
Pericarditis
Muscular
Rhabdomyositis
Rhabdomyolysis with myoglobinuria and
renal failure
Neurological
Encephalitis
Reye’s syndrome
Guillain-Barré syndrome
Transverse myelitis
Systemic
Toxic shock syndrome
Sudden death

10. www.nejm.org June 29, 2009 (10.1056/NEJMoa0904252)
Initial Radiograph of
the Lung and LungTissue Sample
The CXR shows bilateral alveolar
opacities in the base of both lungs that
progressed and became confluent. The
specimen (H&E stain) shows necrosis of
bronchiolar walls (top arrow), a
neutrophilic infiltrate (middle arrow), and
diffuse alveolar damage with prominent
hyaline membranes (bottom arrow).
Bacterial cultures were negative on
admission, and no evidence of bacterial
infection of the lungs was found.
The patient ultimately died.
Pneumonia and Respiratory Failure from Swine-Origin
Influenza A (H1N1) in Mexico

11. WHICH Individual with ILI
needs assessment?
 All individual with ILI and has co-morbid
factors.
 All individuals with moderate to severe
disease
 All individual with symptoms beyond 48
hours.

12. Co-morbidities / Risk factors in
adults
Those considered vulnerable to severe outcomes & should be a focus of
early identification, assessment and treatment, include the following:
 Chronic respiratory conditions, eg asthma, COPD, OSA
 Pregnant women, esp. in second or third trimester
 Obesity (BMI > 30) & morbid obesity (BMI > 40)
 Other predisposing conditions, such as chronic cardiac disease (not
simple HPT), and chronic illnesses including diabetes mellitus, renal
failure, haemoglobinopathies, immunosuppression.
 Adults > 65 years of age esp. those with other chronic diseases
As more epidemiologic & clinical data become available, these risk
groups might be revised.

13. For children with ILI
 Risk factor for severe disease or co-
morbid factors ……..

14. Co-morbid Factors in Children
 Cardiac disease : congenital heart dis.
 Chr. resp. disease : asthma , BPD
 Chronic renal failure
 Haemoglobinopathies
 Diabetes mellitus or other metabolic diseases
 Chr. neurological disease : ms. Dystrophy
 Impaired immunity:HIV,malignancy,Rx
 Malnutrition or obesity
 Children < 5 yrs : Higher risk of severe disease &
mortality

15. Groups vulnerable to the severe outcomes
Vulnerable Group
Evidence
Chronic respiratory conditions eg
asthma esp. those with moderate
persistent disease, COPD, OSA
↑ hospitalisation, ICU admissions
(USA, Mexico, Canada, South
America, UK)
Pregnant women (esp. in 2nd, and
3rd. trimesters)
↑ hospitalisation, ICU admissions,
spontaneous abortion, PROM,
foetal and maternal death ( USA,
Mexico, South America, UK)
Persons with morbid obesity
↑ hospitalisation, ICU admissions
(USA, Mexico,)

16. Obesity & H1N1
 Obesity (BMI > to 30-39.9) noted in about 15% of pts
 Morbid obesity (defined as BMI > 40) in about 8% of pts
 Although the importance of obesity as a contributing factor
to novel H1N1 complications is currently unknown, many
obese persons have other known underlying diseases that
put them at risk for flu complications.
 Series of 10 pts with influenza A (H1N1) virus infection
and ARDS at a tertiary-care ICU in Michigan. Of the 10
pts, 9 were obese ([BMI] ≥30), including 7 who were
extremely obese (BMI ≥40)
MMWR; July 17, 2009 / 58(27);749-752

17. Vulnerable Group
Evidence
Chronic illness predisposing to
severe influenza such as:
• cardiac disease (not simple HPT)
• diabetes mellitus,
• chronic renal disease (GFR <30
mL/min),
• haemoglobinopathies,
• immunosuppressed (including
cancers on active therapy,
HIV/AIDS, regular steroid use)
• chronic neurological conditions
↑ hospitalisation, ICU
admissions
(USA, Mexico,
Canada, South
America, UK)

18. How to recognize disease severity in
an individual with ILI
USE OF CLINICAL
ASSESSMENT TOOL

19. Patients with and any of the following parameters should be considered for
admission to the of nearest hospital
Respiratory impairment: any of the following
Tachypnoea, respiratory rate > 24/min
Inability to complete sentence in one breath
Use of accessory muscles of respiration, supraclavicular recession
Oxygen saturation < 92% on pulse oximetry
Decreased effort tolerance since onset of ILI
Respiratory exhaustion
Chest pains
Evidence of clinical dehydration or clinical shock
Systolic BP < 90mmHg and/or diastolic BP < 60mmHg
Capillary refill time > 2 seconds, reduced skin turgor
Altered Conscious level (esp. in extremes of age)
New confusion, striking agitation or seizures
Other clinical concerns:
Rapidly progressive (esp. high fever > 3 days) or serious atypical illness
Severe & persistent vomiting and diarrhea
Clinical assessment tool for moderate to severe influenza
in adults

20. Moderate-Severe Disease in
children
 Severe respiratory distress
 Increased respiratory rate
 Oxygen sat. < 92% (air or oxygen)
 Absence of cyanosis is a poor
discriminator for severe disease
 Resp. exhaustion or apneic
episode(≥20” pause in breathing)
 Severe dehydration or shock
 Altered conscious level
Clinical assessment tool for children

21. Recognition of moderate to severe
illness & deterioration
Pts with moderate / severe illness, or those who are
deteriorating, whether from vulnerable grp or not, need to be
admitted and provided with antiviral therapy.
Severe illness following influenza occurs in at least 3 ways:
1. severe 1° viral infection with ARDS occurring relatively early
in illness related to viral pneumonia (within 1st 4 days)
2. bacterial pneumonia, complicating initial bronchitis caused by
influenza, or following apparent recovery from initial illness (a
biphasic clinical picture can be obvious)

22. Recognition of moderate to severe
illness & deterioration
3. destabilization of pre-existing chronic condition. This may
present as respiratory distress related to exacerbations of
COPD, asthma or CCF. Influenza can also cause acute
destabilization of diabetes, CRF, chronic liver disease etc.
For children, fit or altered conscious level to indicate
encephalitis is common .

23. Clinical detection of severity of
influenza related illness (1)-adult
Respiratory distress –RR >20–24/min & ↑ work of breathing
 Noticeable respiratory effort, rapid breathing or noisy
breathing in previously normal person at rest is
abnormal. People can adopt different patterns of
breathing when sick, but RR > 20 breaths/min is
concerning (> 24 / min definitely abnormal)
 People with pre-existing lung or heart conditions may
already have some respiratory distress at rest. In
general, this will be greatly accentuated if there are
influenza complications such as exacerbations of COPD,
asthma , CCF or bacterial pneumonia.

24. Clinical detection of severity of
influenza related illness (2)
Abnormal pulse oximetry – Significant ↓in SpO2 (<92%)
 Measurement of a low SpO2 can detect severe or
complicated influenza in some cases. Most useful in
people with pre-existing heart / lung conditions who
already have reduced SpO2 (eg ≤ 92%); slight worsening
of respiratory function due to influenza will cause
significant fall in SpO2 < 90%.
 In people with normal pre-existing respiratory and cardiac
function, SpO2 < mid 90’s is abnormal and < low 90s is
very abnormal and indicates severe disease.
Due to individual patient’s ability to compensate, always correlate SpO2
with clinical condition of patient (esp. if SPO² is normal)

25. Clinical detection of severity of
influenza related illness (3)
Generalised organ dysfunction – ↓ baseline function or exercise
capacity
 “Loss of function” includes confusion, incontinence & falls:
common features of severe influenza and pneumonia in
elderly. Hypotension, marked tachycardia & hyperthermia
or hypothermia are features of significant sepsis. Diabetics
with severe influenza can present with hyperglycemia .
 “↓ effort capacity” – If significantly ↓ because of worsening
breathlessness during influenza, possibility of respiratory
complications should be considered.

26. HOW ABOUT CHILDREN?

27. Sx of Severe Disease in
Children
 Apnea
 Tachypnea
 Dyspnea
 Cyanosis
 Dehydration
 Altered mental status
 Extreme irritability
Source :www. cdc.gov/h1n1flu/

28. Severe Respiratory Distress in
Children-1
 Lower chest wall indrawing
 Sternal recession
 Grunting
 Noisy breathing when calm

29. Increased Respiratory Rate in
Children-2
 Measured over at least 30”
 ≥ 50 breaths per min if under 1 yr old
 ≥ 40 breaths per min if ≥ 1 year old
Source : Dept of Health UK , 2009

30. Severe Clinical Dehydration
or Clinical Shock in children-3
 Capillary refill time ≥ 2”
 Reduced skin turgor
 Sunken eyes or fontanelle

31. CNS Involvement in children-4
 Irritable
 Unconscious
 Drowsiness
 Confusion
 Seizures
 Weakness or paralysis
 Floppy infant

32. Assessment of Conscious
Level in a child
 Alert
 Responds only to voice
 Responds only to pain
 Unresponsive
 Score of P or U correspond to GCS <8 &
suggest urgent referral to hospital
Source : Paediatric Intensive Care Society UK 2009

33. RECOMMENDATION:
Who needs medical assessment?
Patients with ILI:
 who have moderate or severe illness (based on the Home
Assessment Tool)
OR
 who have significant co-morbidities and hence are at high risk
for complications from influenza
OR
 who have fever (≥38°C) after 48 hrs from illness onset
should seek EARLY professional medical assessment (preferably
within first 2 days of illness) from the nearest hospital or
health clinic (depending on severity of symptoms

34. Individuals with ILI
 Who needs admissions?

35. Patients to be hospitalized for
novel influenza A / H1N1 virus
The following patients will be admitted to the flu ward /
cubicle of the hospital:
 All patients fulfilling criteria of ILI with any of the
parameters listed in the clinical assessment tool for
moderate to severe influenza (with or without comorbidities)
Patients with suspected influenza manifesting with mild disease will not
require admission to hospital
Patients should be clinically assessed and the admission decision will be
based on the severity of the illness.
All individual with ILI and does not require admission need to be
informed of how to recognize disease deterioration. Use of home
assessment tool informed to all.

36. Patient Home Assessment Tooladults
Patients with ILI are advised to seek medical care should
they develop any of the symptoms & signs listed as below :
1
Respiratory Difficulties: Shortness of breath, rapid breathing
or Purple or blue discoloration of lips
2
Coughing out blood or blood streaked sputum
3
Persistent chest pains
4
Persistent diarrhea and / or vomiting
5
Fever persisting beyond 2 days or recurring after 2 days
6
Abnormal behavior , confusion, less responsive , convulsion
7
Dizziness when standing and/or reduced urine production

37. Home Assessment Tool for
Parents & Caregivers(pediatrics)
 Lethargy or poor oral intake
 Change in mental status or behavior
 Signs of dehydration
 Signs of respiratory distress
 Fits
 Cyanosis
 Persistent fever > 2 days

38. Laboratory test
 Who needs to be tested?
 What test?
 How about rapid test Vs RT-PCR for
H1N1

39. RECOMMENDATION:
Who needs to be Tested?
Laboratory testing (RT-PCR) for Influenza A H1N1 to
assist with clinical management is indicated for those
who meet the case definition for ILI * and are:
 symptomatic patients with moderate to severe
disease (see clinical assessment tool below) who will
require hospitalization
* Influenza-like-illness (ILI) is defined as fever (esp. temperature > 38°C) and a
cough and/or a sore throat in the absence of a KNOWN cause other than influenza

40. Confirmed Case novel
Influenza A/H1N1 Infection

Individuals with ILI and +ve laboratory
test , either by
RT-PCR
b) Viral culture
In Malaysia, the usual test to detect this
novel virus is RT-PCR .
a)

41. How about rapid test?
 Rapid test : use to detect the presence
of Influenza A virus in respiratory
specimens.
 A positive rapid test means-presence of
Flu A virus.
 Does not differentiate between seasonal
flu or Influenza A-H1N1.
 Detection rate varies from one test kit to
another.
 A negative test does not rule out
Influenza virus infection

42. Defining the cause of the severe
clinical illness (1)
Severe influenza
 primary viral pneumonia or viral-induced acute lung injury
usually occur within the first 4 days of the illness and are
associated with respiratory distress and sometimes a dry
cough, along with fever and the other symptoms of influenza
like illness (ILI).
 Bacterial pneumonia – important complication of pandemic
influenza and presents as a biphasic illness with features of
an ILI followed by 2nd. rise in T° or a persistent fever (>3
days from onset of ILI) with purulent sputum.

43. Defining the cause of the severe
clinical illness (2)
Pneumonia
 Distinguishing between acute bacterial bronchitis and
bronchopneumonia without CXR can be difficult. High
persistent fever, pleuritic chest pain and respiratory distress
all suggest pneumonia. In the setting of an influenza
pandemic, development of purulent sputum should trigger
the use of empiric antibiotics (choice as in National Antibiotic
Guidelines / standard guidelines)
 Initial low or normal TWBC followed by neutrophilia with
persistent (or recurrence) of fever may suggest a bacterial
complication often a pneumonia

44. Sputum production
 Purulent sputum - in normal people, green or
yellow sputum correlates reasonably well with
bacterial bronchitis or pneumonia.
 ↑ volume of sputum or deepening colour (dark
yellow / green) of sputum in a COPD pt also
correlates with bacterial infection.
 People with asthma can produce coloured
sputum due to eosinophilic inflammation, but
in context of an AEBA triggered by influenza,
2° bacterial infection should be considered.
 This is more so in adults and older children

45. Antiviral Treatment for Novel
Influenza A / H1N1
RECOMMENDATION:
Antiviral Treatment is recommended for:
All hospitalized patients (ie. those with moderate to severe
disease) with confirmed or suspected novel influenza A
H1N1. Empirical therapy for suspected patients with severe
disease should be considered if the turnaround time for
H1N1 confirmation is prolonged. The antiviral treatment
maybe stopped if the results are negative.
All individual with co-morbid factors whether they are admitted
or not.

46. Antiviral Therapy
 Type of Antiviral: Oseltamivir is the preferred choice; zanamivir
might be used as an alternative. The quality of evidence if
considered on a continuum, is lower for zanamivir compared to
oseltamivir.
Since functional groups of the 2 neuraminidase-inhibitors have differences in their
binding sites, mutants resistant to 1 drug maybe susceptible to the other.
Oseltamivir dosage:
 Duration 5 days
 Adults & adolescents > 13 yrs:
75 mg bd
(in severe cases, dosage can be doubled to 150 mg bd)
 For children (according to weight): <15kg: 30mg bd
15-23kg: 45mg bd
23-40kg: 60mg bd
> 40kg: 75mg bd
Renal adjustments: patients with a serum creatinine clearance between 10 30 ml/min: treated with 75 mg daily for 5 days

47. Antiviral Therapy
 Zanamivir dosage:
10mg (2 puffs) bd for 5days (Adults & children)
(Children < 5 yrs may have difficulty with Diskhaler)
 In patients with bronchospasm: Zanamivir is not
recommended for the treatment of patients with underlying
airways disease (eg. asthma or COPD). Patients with
pulmonary dysfunction should always have a fast-acting
bronchodilator available and discontinue zanamivir if
respiratory difficulty develops.
 No dosage adjustment is required in patients with renal
impairment

48. Patient presenting with ILI
symptoms within 2 days of onset
of illness
Assessed by Primary doctor
Does patient have any symptoms and
signs of moderate or severe illness
(Clinical assessment Tool)
Managing ILI
patients in the
outpatient
setting
If NO moderate/severe illness;
Does patient have a co-morbidity
associated with increased risk of
influenza complications?
If patient HAS moderate or severe
illness;
Admit to nearest hospital for
screening and treatment
If patient has co-morbidity ;
Start oseltamivir / zanamivir at
standard doses for 5 days & continue
home care with Home assessment
Tool monitoring
If patient has NO comorbidity;
Does patient have fever > 38°C after
48hours from onset of illness ?
Are symptoms rapidly progressive
even within first 2days?
If patient develops moderate or
severe illness with Home Assessment
Tool, seek medical reassessment
If patient improves, complete course
of antivirals
If YES to either of the above; start
oseltamivir / zanamivir at standard
doses for 5 days & continue with
Home Assessment Tool

49. child with ILI symptoms
within 48 hours of onset of
illness
Assessed by Primary doctor
•Does patient have any
symptoms and signs of
moderate or severe illness
(Clinical assessment Tool**)
NO
Does y CO-MORBIDITIES?
With comorbidities
Start oseltamivir treatment
following the pediatric
dosages guideline for 5
days and sent patients
home with ***Home
Assessment Tools
If patient developed
moderate to severe
symptoms (following Home
Assessment Tool), to admit
patient to hospital for
screening and treatment.
YES
Admit to hospital for
screening and
treatment
No comorbidities
Symptomatic
treatment and sent
home with ***Home
Assessment Tools
Managing ILI in
children at out
patient settings

50. Oseltamivir
Side Effects
 Gastrointestinal(40%) : nausea ,
vomiting , stomach pain/cramps,
diarrhea
 Neuropsychiatric(18%) : sleep
problems , insomnia , poor concentration
, delirium , feeling confused ,
hallucinations , bad dreams , nightmares
, abnormal behavior
Source : Eurosurveillance 2009;14:1-4

51. Why only certain individual is
given antiviral and not all
 Indiscriminate use of antiviral can cause
the virus to be resistance
 Drug has side-effects
 For children, the side effects is more
pronounced in infant less than 1 year(
the use of oseltamivir in child less than 1
year is EUA)

52. Viruses resistant to oseltamivir
identified: 20th. August 2009
 WHO: notified of 12 cases of oseltamivir resistant virus.
 mutation in the neuraminidase (H275Y) that confers
resistance to oseltamivir, though the viruses remain
sensitive to zanamivir.
 Of these , 8 assoc. with oseltamivir post exposure
prophylaxis, 1 with treatment of uncomplicated illness, and
2 from immunocompromised pts receiving oseltamivir tx.
 Japan 4, USA 2, China, Hong Kong SAR China 2, and 1 in
Denmark, Canada, Singapore and China.
 There is also no evidence of onward transmission from
these cases.

53. Conclusions
 Careful clinical assessment of the
individual with ILI in primary healthcare
setting is imperative
 Admission is needed for individual with
moderate to severe diseases of any age.
 Treatment with antiviral is needed only
for admitted individuals and those with
co-morbid factors whether admitted or
not.

54. Conclusions
 Parents should be duly advised on home
monitoring for those children Rx as
outpatient
 Same goes for adults with ILI
 Antiviral recommended for at-risk
children and adults is usually
oseltamivir(Tami flu)